Natural insect repellent

ABSTRACT

A topical insect repellent with extended duration of protection was obtained from mixtures of molecules based on two or more volatile repellent organic molecular species occurring naturally on the human skin surface. The novel repellent comprises mixtures of lower, intermediate, and higher volatility organic molecules. Active ingredients for formulations are obtained from homologous series of carboxylic acids, alcohols, ketones, and lactones which span a similar range of volatility and which occur naturally on the skin surface. Volatile silicone fluid imparts mildness and water repellency to the repellent formulations. The new natural repellent exhibits the longevity and repellency that is comparable to N,N-diethyl-m-toluamide (DEET), a synthetic compound employed in almost all commercial formulations, but the inventive natural repellent is more acceptable than DEET, which has an unpleasant odor and imparts a greasy feel to the skin. The inventive insect repellent, formulated in a volatile silicone fluid, was shown to repel and incapcitate stable flies. This finding demonstrated that repellency was not limited to mosquitoes, but extends to other biting flies or insects, thus demonstrating the utility of the novel insect repellent for protecting pets and livestock as well as humans.

This application is a continuation of non-provisional U.S. patentapplication Ser. No. 09/107,700, filed Jun. 30, 1998, now U.S. Pat. No.6,306,415 B 1 which is herein incorporated by reference in its entiretyfor all purposes. This application also claims the benefit of prior U.S.application Ser. No. 60/051,320, filed Jun. 30, 1997 and is hereinincorporated by reference.

I. BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to insect and arthropod repellents andmore specifically to mosquito, fly, tick and mite repellents usingbiologically based components.

2. Description of Related Art

At the present time, N,N,-diethyl-m-toluamide (DEET) is the activeingredient of most commercial topical insect repellents (see Table 1,below), and the current US Army insect repellent (EDTIAR) contains DEETas its active ingredient. The major commercial brands, Off!®, “DeepWoods Off!®, and Cutter®, are all DEET based products and comprise 85%of insect repellent sales (Consumer Reports Buying Guide, 1994 SpecialYear-End Issue). Consumer Reports tests indicated that products with thehighest concentration of DEET lasted the longest against mosquitoes, butcautioned that excessive use of DEET could pose some risk, especiallyfor children. Other disadvantages associated with DEET include: It is asynthetic chemical having a limited spectrum of activity and anoticeably unpleasant odor; DEET is a powerful plasticizer and willdissolve or mar many plastics and painted surfaces; DEET plasticizes theinert ingredients typically used in topical formulations in order tolengthen the time of effectiveness. This leads to DEET formulations withlow user acceptability.

TABLE 1 Commercial Topical Insect Repellents Product ManufacturerIngredients Ben's Backyard ® Tender DEET, 23% Ben's Max ® Tender DEET,95% Cutter Insect Repellent ® Miles Inc. DEET, 21.85% Muskol MaximumStrength ® Schering- DEET, 100% Plough Muskol Ultra ® Schering- DEET,38% Plough Natrapel ® Tender Citronella oil, 10% Off Deep Wood Formula ®S. C. Johnson DEET, 28.5% Off Skintastic Insect S. C. Johnson DEET,7.125% Repellent ® Off Spring Fresh ® S. C. Johnson DEET, 14.25%

In recent years, a proprietary bath oil (Skin-So-Soft®, Avon Products,Inc., New York) has been used as a topical insect repellent. Two of itsingredients (diisopropyl adipate and benzophenone) are repellent toAedes aegypti (King, W. V. 1954. Chemicals evaluated as insecticides andrepellents at Orlando, Fla. U.S. Dept. of Agriculture, AgricultureHandbook No. 69:1-397). However, the bath oil was reported as lesseffective and less persistent than DEET (Rutledge et al., 1982,Repellent activity of a proprietary bath oil (Skin-So-Soft), MosquitoNews:42:557-559).

Efforts to develop a natural insect repellent have motivated studies ofoils of citronella, turpentine, pennyroyal, cedarwood, eucalyptus andwintergreen, but these are relatively ineffective (Handbook ofNonprescription Drugs, 1993, 10th Ed., American Pharmaceutical Assn.,Washington, D.C.). Consumer Reports tests indicated that “naturalproducts” and products without DEET, including Skin-So-Soft®, providedlittle or no protection against mosquitoes (Consumer Reports BuyingGuide, 1994 Special Year-End Issue). Insect repellents fornonprescription oral use are not generally recognized as safe andeffective (Federal Register, 1985, 50:25170).

Franz Bencsits describes “Use of First Runnings Coconut Fatty Acid asInsect-repellent” in U.S. Pat. No. 5,594,029. Although Bencsits does notdescribe specifically what “first runnings” of coconut fatty acids are,he describes that combining the “first runnings” with “. . . anotheractive substance, an oil or fat selected from the group consisting ofrape-seed oil, sunflower oil, peanut oil/butter, . . . ” etc. providesan insect repellent. Because the term “first runnings” is not a term ofart and is not understood by the average knowledgeable person working inthe field, it is impossible to know exactly what substance Bencsitstested. The average knowledgeable person working in the field offormulating insect repellents does not know what “first runnings” are orhow to obtain them. Many experts also do not understand this term andwere not able to discover its meaning even with research. Furthermore,the limited number of tests and controls, and lack of attention to fattyacids as potential skin irritants appear to limit Bencsits' invention tonon-animal surfaces.

Bencsits teaches the use of up to 15% potassium hydroxide (KOH) in hisformulations. KOH ionizes fatty acids, turning them into non-volatilesalts. Bencsits thus teaches away from the utility of volatilecompounds.

Bernard Crammer, et al. Describes in U.S. Pat. No. 5,064,859, a methodfor killing lice and lice eggs that have infested human skin and hairwith a C₈ to C₁₂ alkyl radical. The patent does not mention repellinglive approaching insects.

Stephen Herman describes, in U.S. Pat. No. 5,093,326, a compositioncomprising an ozonized derivative of unsaturated hydrocarbon forrepelling insects from a surface. Performance does not appearcompetitive with DEET.

Clearly there is a need for a long-lasting effective insect repellentthat is pleasant to use and that will not damage plastic containers, orthe text printed on the containers.

II. SUMMARY OF THE INVENTION

It is an object of the present invention to provide an insect andarthropod repellent that is safe, long-lasting, effective and pleasant.It is a further object for the inventive formulation to avoid the damageto plastic containers and the text printed on the containers that isassociated with currently effective insect repellent formulations.

The present inventive insect and arthropod repellent comprises acombination of two or more homologous volatile repellent molecules,similar or identical to those normally found on human skin, wherein atleast one of the molecules has a vapor pressure between about 0.1 mm Hgand about 10 mm Hg at 125° C. and at least one other molecule has avapor pressure between about 5 mm Hg and about 100 mm Hg at 125° C.

III. SUMMARY DESCRIPTION OF THE DRAWINGS

FIG. 1: illustrates the evaporation rate of such a hypotheticallong-lasting repellent having a relatively constant evaporation ratesufficiently above the MEER to maintain effective repellency.

FIG. 2: shows schematic diagram of a Skin Penetration/Evaporationlaboratory apparatus.

FIG. 3: shows the percent repellency of homologs containing 8 to 11carbon atoms applied to gauze, compared to DEET.

FIG. 4: shows the percent repellency of homologs containing 8 to 11carbon atoms applied to skin, compared to DEET. The repellency droppeddramatically with increasing numbers of carbon atoms.

FIG. 5: shows a graph of percent repellency two hours after skinapplication. 4-methyloctanoic acid (4MOCTAN) and nonanoic acid (C9) hadthe highest repellency.

FIG. 6: shows a graph comparing the percent repellency of 0.3 and 0.6mg/cm² 4MOCTAN and 0.3 mg/cm² DEET over a 4 hour period. Taking intoconsideration that about 50% of the 4MOCTAN ionizes at skin pH, therepellency of 4MOCTAN is nearly equal to that of DEET.

FIG. 7a: shows a graph of percent repellency vs. time for each of thethree molecules, octanoic acid C8, nonanoic acid C9, and decanoic acidC10 compared to DEET.

FIG. 7b: shows a graph of percent repellency vs. time for a 1:1:1mixture of octanoic acid (C8), nonanoic acid (C9), and decanoic acid(C10), each at a topical dose of 0.2 mg/cm², and 0.3 mg/cm² DEET. TheC8C9C10 combination gave repellency at 8 hours after applicationcomparable to that of DEET at 4 hours.

FIG. 8: shows a diagram of a modified Feinsod-Spielman olfactometer.

FIG. 9: shows a histogram of olfactometer scores, which measureattractancy of female test subjects. A higher number designates greaterattractancy.

FIG. 10: shows a histogram of olfactometer scores, which measureattractancy of male test subjects. A higher number designates greaterattractancy.

FIG. 11: shows a plot of female test subject olfactometer scores, whichmeasure attractancy, vs. age.

FIG. 12: shows a plot of male test subject olfactometer scores, whichmeasure attractancy, vs. age.

FIG. 13: shows the change in evaporation rate of DEET over time, and ofa mixture of equal concentrations of C₈, C₉, and C₁₀; the straight linerepresents the minimum effective evaporation rate for DEET.

FIG. 14: shows a comparison of the repellency of formulated C8C9C10 vsSkintastic against Aedes aegypti mosquitoes.

IV. DETAILED DESCRIPTION OF THE INVENTION

The present invention comprises an inventive formulation for applicationto skin that has a natural pleasant feel, which is made from fatty acidsor other organic molecular species normally found on many people's skin,and which is approximately as effective as DEET both in terms ofrepellency and duration of effect. The active repellent molecules have apolar group attached to a non-polar group comprising between about threeand about twelve carbon atoms. The non-polar group may comprise abranched carbon chain or an unbranched carbon chain. The polar group maycomprise carboxyl, alcohol, ketone, lactone or other polar groups. Aneffective formulation or composition or repellent molecules comprisesmolecules having at least two different volatilities. To achieve such amixture, homologous molecules having different lengths unbranched carbonchains can be used because shorter unbranched carbon chains are morevolatile than longer unbranched carbon chains. Another method ofachieving a mixture of volatilities is to mix homologous moleculeshaving a branched non-polar chain with molecules having different (orno) branching configurations of the same number of carbons. It will beobvious to chemists of ordinary skill that a mixture comprising variousother combinations of homologs and isomers of an active repellentmolecule will result in a combination of volatilities.

The inventive formulation comprises a combination of two or morehomologous volatile repellent molecules, similar or identical to thosenormally found on human skin, wherein at least one of the molecules hasa vapor pressure between about 0.1 mm Hg and about 10 mm Hg at 125° C.and at least one other molecule has a vapor pressure between about 5 mmHg and about 100 mm Hg at 125° C. Preferably the molecules are freefatty acid carbon chains having between 3 and 12 carbon atoms and apolar group on one end.

Preferably the repellant molecules are mixed in a dermatologicallyacceptable carrier. The carrier allows the formulation to be adjusted toan effective concentration of repellant molecules. The carrier mayfurther provide water repellency, prevent skin irritation, and/or sootheand condition skin. For example the carrier may include silicone,petrolatum, lanolin or many of several other well know carriercomponents.

Insect repellents form an unusual class of compounds where evaporationof the active ingredient from the skin surface is necessary foreffectiveness. An evaporation rate greater than the minimum effectiveevaporation rate (MEER) results in a significant and undesirable mode ofloss. Penetration into and through the skin is also an undesirable modeof loss of compound from the skin surface. In the past, researchersattempted to balance these properties by finding a single activeingredient having the right balance of physical properties.Alternatively, the active ingredient was formulated with polymers andinert ingredients added to the active ingredient for the purpose ofmodifying the persistence of the active ingredient on the skin surface.Adding inert ingredients to the active ingredient limits the number ofmolecules of active ingredient on the surface of the repellent film.Since a molecule must be on the surface in order to evaporate, theevaporation rate is lowered. This carries with it the negativeconsequence of diluting the concentration of active ingredient that canbe applied to the skin which in turn reduces the overall potency of aformulation containing inert ingredients. In another alternative, theactive ingredient was contained in microcapsules to control rates ofloss from the skin surface. Another technique of limiting theevaporation rate of active ingredient was to synthesize a precursormolecule, which slowly disintegrated on the skin surface to release theactive ingredient.

Desirable properties of a topical insect repellent include low toxicity,resistance to loss by water immersion or sweating, low or no odor or atleast a pleasant odor, ease of application, and rapid formation of a drytack-free surface film. Attempts to improve the properties of DEETthrough polymer or microcapsule formulation have been frustrated byDEET's plasticizing properties, which lead to a high tack skin surface.

The present invention makes use of a novel method of developing a anoptimal topical repellent, firstly by deriving the active ingredientsfrom chemicals already naturally found on the skin and secondly, byusing homologs of the active ingredient to optimize evaporation rate.Since the homologs also possess repellent activity, as opposed to inertingredients which do not, the amount of active repellent on the skinsurface is maximized.

When formulating the insect repellent composition it is important tocombine a volume repellent molecules having relatively high volatilitieswith a volume of repellent molecules having a lower volatility whichwill remain on the skin longer. One way to achieve a mixture ofvolatilities is to mix organic molecules having unbranched chains ofdiffering chain lengths, that is mixing shorter carbon chains which aremore volatile with longer carbon chains. Preferably the shorter chainshave between about 6 and about 8 carbon atoms per molecule. Preferablythe longer chains have between about 9 and about 12 carbon atoms permolecule.

A wide variety of compounds possess insect repellent and/or mosquitorepellent activity, as evidenced by the diversity of chemical structuresreported by the USDA (Chemicals Evaluated as Insecticides and Repellentsat Orlando, Fla., compiled by W. V. King, US Department of Agriculture,Agricultural Research Service, Agriculture Handbook No. 69) to containrepellent activity. Activity is found in alcohols, amides, esters,ketones, acids, lactones, lactams etc., and positional isomers of DEETor the diasterioisomers of ethyl hexanediol, both well studiedrepellents, have similar repellent activity. Activity does appear todepend on the physical properties of these compounds. One property thatis important is surface activity, as most, if not all, repellentscontain both polar and non-polar regions in their structure. A secondproperty is volatility. Because mosquitoes' sensory receptors formosquito repellents such as DEET are located on the mosquito antenna,effectiveness of a repellent compound depends on it's volatility fromthe skin surface. It is desirable for the repellent compound to reachthe mosquito antenna before the mosquito lands on the skin. Whenmosquitoes' antenna are removed, they are not repelled by DEET. Manyyears of observations of mosquito behavior reveal that biting occursshortly after mosquitoes begin to land on repellent treated skin.

Therefore, the evaporation rate of repellents from the skin surface isan extremely important factor in the ability of repellents to protectthe skin from bites. A certain minimum concentration of repellent isneeded in the air space directly above the skin surface in order torepel insects, and this concentration is a measure of the potency of therepellent. To maintain this concentration, each repellent must have aminimum effective evaporation rate (MEER) from the skin surface. TheMEER will change as a function of conditions in the field. For example,as the avidity or biting tendency of a mosquito increases, a higher MEERwill be required. Another important factor that influences the MEER isthe concentration of mosquitoes. For example, in an environment having alow concentration of mosquitoes where those mosquitoes were not hungry,the MEER could be as low as 2, or more commonly 5, or 6. In anenvironment having a high concentration of hungry mosquitoes the MEERmight be as high as 12 or even 15. In many environments, a MEER of about9 or 10 is required, as indicated in FIG. 1.

The evaporation rate of a compound from the surface of the pure liquidwill be a function of its vapor pressure (VP) and molecular weight (M),as given by equation (1), where f is a constant (W. F. Spencer and W. J.Farmer, Assessment of the Vapor Behavior of Toxic Organic Chemicals, inDynamics, Exposure and Hazard Assessment of Toxic Chemicals, R Haque,ed, Ann Arbor (1980), pp. 143-161).

Evaporation rate (bulk liquid)=f(VP)(M)^(0.5)   (1)

When a repellent is applied in small doses to the skin surface, theevaporation rate is determined by many factors, including the rate ofskin absorption. The evaporation rate will decrease with time (t) inproportion to the amount of chemical remaining on the skin surface andcan be approximated by equation (2), where A is the evaporation rate att=0 and e and k are constants.

Evaporation rate (skin surface)=Ae ^(−kt)   (2)

At a certain time point (t_(d)) after topical application, theevaporation rate of a repellent from skin becomes less than the MEER andbiting will occur. The time t_(d) represents the effective duration ofrepellent protection. A long lasting repellent for the skin would havean a relatively constant evaporation rate (a low value of “k” inequation 2) that is sufficiently above the MEER. FIG. 1 illustrates theevaporation rate of such a hypothetical repellent. The insect repellentDEET was the result of an intensive search by the USDA to find such acompound. Unfortunately though, DEET repellency varies with itsevaporation rate, which can be different in a laboratory instrument suchas the “Skin Penetration/Evaporation Apparatus” shown in FIG. 2 and inreal field conditions. Measured with the apparatus shown in FIG. 2,DEET's evaporation rate immediately after application is much higherthan the MEER; the rate decreases rapidly thereafter. Under laboratoryconditions DEET provides only 5-7 hours of protection and much less thanthat under summer field conditions.

Many attempts have been made to formulate DEET with inert ingredients toreduce its initially excessive rate of evaporative and to extend thetime interval when the evaporation rate is above the MEER. However, DEETplasticizes or partially dissolves many of these materials, renderingthem ineffective or creating a sticky formulation unacceptable for useon the skin. This approach also suffers from the fact that only acertain total amount of repellent formulation can be applied to the skinsurface and that the addition of inert ingredients to the formulationdecreases the amount of active that can be applied. Generally, the ratio(by weight) of added inert ingredient to DEET must be at least 3-4before the additive begins to significantly affect DEET's evaporationrate (Evaporation and Skin Penetration Characteristics of MosquitoRepellent Formulations, W. G. Reifenrath, G. S. Hawkins and M. S. Kurtz,J. Am. Mosq. Control Assn., 5:45-51, 1989).

Naturally occurring fatty acids contain both polar (carboxylic acidgroup) and non-polar (alkyl chain) regions in their structure and thelower molecular weight homologs are sufficiently volatile to evaporatefrom the skin surface. Individually, these compounds have repellentactivity. A number of these compounds were applied to non-absorptivegauze mounted between the human forearm and the olfactometer containingmosquitoes. These tests were done immediately after application tominimize losses due to evaporation (described fully in “Example 2”below). Because skin absorption and evaporative loss is minimized, thistest can be regarded as a measure of the potency of the compounds.Homologs containing 8 to 11 carbon atoms had similar potency (percentrepellency), which was greater than that of DEET (FIG. 3). Six carbonhomologs and twelve carbon homologs had potency equal to or less thanDEET. These results focused attention on carboxylic acids containing sixto twelve carbon atoms. When the repellency of compounds within thisrange was determined immediately after application to skin (described inExample 2, below), only the saturated derivatives octanoic acid (C8) and4-methyloctanoic acid (4MOCTAN) had repellency comparable to DEET andthe unsaturated derivatives 2-octenoic acid (2OCTEN) and3-methyl-2-octenoic acid (3M2OCTEN) were less repellent (FIG. 4).Percent repellency dropped dramatically with increasing numbers ofcarbon atoms in the molecule (FIG. 4). Two hours after skin 2application, 4-methyloctanoic acid (4MOCTAN) and nonanoic acid (C9) hadthe highest repellency (FIG. 5). The nonanoic acid was preferablysaturated. 4MOCTAN had the best overall performance at the zero and twohour time points. It should be noted for FIGS. 4 and 5 that thecarboxylic acids exist on the skin at a pH which ionizes 50% of themolecules (pH=pKa of the acids). Since the ionized species are notvolatile, the actual available dose is approximately 50% of that forDEET. Taking this factor into consideration, the repellency of 4MOCTANat 0.6 mg/cm² is nearly equal to that of DEET over a 4 hour period (FIG.6). However, 4MOCTAN is thermally unstable and is not generallyavailable commercially.

Rather than conduct a time-intensive search for a single carboxylic acidwith optimal repellent properties and user acceptability (many shortchain fatty acids have very strong, objectionable odors), a mixture ofrepellent fatty acids spanning a range of volatility was investigated.In theory, molecules in a mixture “compete” with each other forevaporative loss from the skin surface, and the initial evaporation rateof each component will be lower than that of an equal dose of purecomponent. Initially, each component would be expected to undergoapproximately the same percentage reduction in evaporation rate if thecomponents are present in equal amounts. The component with the highestvapor pressure will have the greatest reduction in component massentering the air space over the skin. At later time points, theevaporation rate of each component will be higher than that of an equaldose of pure component. Again, the component with the highest vaporpressure will have the greatest increase in component mass entering theair space over the skin. Mixing less volatile, but still active, longerchains with the more volatile shorter chains, results in a constantevaporation of active repellent molecules from the surface of the filmof the inventive insect and arthropod repellent after it is applied tothe skin, hair or clothing of the user. The net result of the mixturewill be reduction in the initial excessive evaporation of the mostvolatile repellent component and, at longer time points, a higher totalrate of evaporation of repellent molecules into the air space over theskin. Such a result will lead to a composition with extended duration ofprotection. Specifically, we found that a 1:1:1 mixture of octanoic acid(C8), nonanoic acid (C9), and decanoic acid (C10), each at a topicaldose of 0.2 mg/cm², was found to give repellency at 8 hours afterapplication comparable to that of DEET at 4 hours. FIG. 7A shows thepercent repellency of each component by itself, and FIG. 7B shows thepercent repellency of the inventive repellent combining two or moremolecules having different volatilities. An additional advantage of thismixture is the ability to easily change the ratio of components to suitconditions. If mosquito avidity or biting pressure is very high (theFlorida everglades, for example), the mixture may fail immediatelybecause the initial evaporation rate does not exceed the MEER. In thiscase, the proportion of C8, the most volatile component, could beincreased to provide effective repellency, although some loss ofduration would be expected.

The relative concentrations of molecules having more and less volatilityused in a particular formulation can vary greatly depending on the needsof the user. Where it is easy to reapply repellent, a higher percent ofthe shorter, more volatile molecules is used; where it is important tohave long lasting protection, a high percent of the longer, lessvolatile molecule is used.

As stated above, the shorter chains preferably have between about 6 andabout 8 carbon atoms per molecule and the longer chains preferably havebetween about 8 and about 12 carbon atoms per molecule.

For example, the shorter chain component can vary between 1% and 99% ofthe active ingredients. More preferably it varies between about 10% andabout 90% of the active ingredients. Alternatively, it varies betweenabout 40% and about 60% of the active ingredients. The longer chaincomponent can also vary between 1% and 99% of the active ingredients.More preferably it varies between about 10% and about 90% of the activeingredients. Alternatively, it varies between about 40% and about 60% ofthe active ingredients.

For many application it is most desirable to have three or morevolatility ranges present in the active ingredients. One example wouldbe a mixture in which relatively short, intermediate, and long chainswould be present. The percentages with which these components are mixedfor a given application will quickly become apparent to one of ordinaryskill in the art. When mixing more than two unbranched chain sizes inthe repellent, the shorter chain component preferably has between about6 and about 8 carbon atoms per molecule, the intermediate chaincomponent has between about 8 and about 9 carbons per molecule, and therelatively longer chain component has between about 9 and about 12carbons per molecule.

The high volatility component can vary between 1% and 99% of the activeingredients. More preferably it varies between about 10% and about 70%of the active ingredients. Alternatively, it varies between about 20%and about 50% of the active ingredients. The intermediate volatilitycomponent can vary between 1% and 99% of the active ingredients. Morepreferably it varies between about 10% and about 70% of the activeingredients. Alternatively, it varies between about 20% and about 50% ofthe active ingredients. The lowest volatility component can vary between1% and 99% of the active ingredients. More preferably it varies betweenabout 10% and about 70% of the active ingredients. Alternatively, itvaries between about 20% and about 50% of the active ingredients.

Among molecules having unbranched carbon chains, those molecules havingshorter chains have higher volatility than longer chains. Additionalmodifications in volatility of the component compounds are made bymodifying the branching of the chains. Generally branching on a chainincreases volatility.

The inventive repellent comprises a novel combination of organicmolecules, having different evaporation rates, where vapor pressure isrelated to the evaporation rate. Thus, one formulation of the inventiverepellent comprises a mixture of three straight chain molecules, such asoctanoic acid, nonanoic acid, and decanoic acid. An alternateformulation comprises a mixture of, for example, straight chain C-10(decanoic acid) combined with branched ten-carbon molecules such as4-methyl nonanoic acid. Any combination organic molecules having theappropriate volatilities to balance immediate and long-termeffectiveness may be used to formulate the inventive repellent. Straightchain and branched chain organic molecules are combined to achieve thisbalance as well as combinations of straight-chain lengths orbranched-chain molecules having the same or different numbers ofcarbons. The choice of which organic molecules to use in the inventiverepellent is governed by factors such as commercial availability, cost,repellency, evaporation rate, odor, and stability.

Review of literature in the general field of the invention:

There is ample evidence that human skin emanates both attractant andrepellent compounds for mosquitoes. No single compound is likelyresponsible for mosquito attraction; the same can be said for mosquitorepulsion. The interaction of these compounds is probably of importancein the overall response of the mosquito. Brown (Brown A. W. A., H. P.Roessler, E. Y. Lipsitz and A. G. Carmichael. Factors in theattractiveness of bodies for mosquitoes. The Canadian Entomologist96:102-103, 1964.) lists a number of factors involved in the attractionof mosquito to man (in order of importance): moisture, convective heat,carbon dioxide, movement, contour or increase in black-white interfaces,and reflectivity. The influence of carbon dioxide as a mosquito“activator” has long been recognized (Rudolphs, W. Chemotropism ofmosquitoes. New Jersey Agricultural Experiment Station Bulletin No. 367,1922). However, Acree and coworkers (Acree, F, R. B. Turner, H. K.Gouck, M. Beroza and N. Smith. L-Lactic Acid: A mosquito attractantisolated from humans. Science, 161:3846-7, 1968) have shown that carbondioxide does not attract mosquitoes in purified air alone. Thiel andLaarman found that air swept over the arm was attractive even thoughcarbon dioxide and moisture had been removed; they concluded thepresence of other attractants or odors was responsible for theattraction (Van Thiel, P. H. and J. J. Laarman. What are the reactionsby which the female Anopheles find its blood supplies? Acta Leidensia24:180-187, 1954). Snow (Snow, W. F. The effect of a reduction inexpired carbon dioxide on the attractiveness of human subjects tomosquitoes, Bull. Ent. Res. 69:43-48, 1970) studied mosquito attractionto normal subjects and to subjects wearing a breathing apparatus toremove most of the exhaled carbon dioxide. Fewer mosquitoes wereattracted to the subjects with reduced carbon dioxide output. However,when the mosquitoes were in close range of the host, the experimentaltreatment had no effect on the proportion of mosquitoes attempting tofeed. Snow concludes from this study that carbon dioxide, originatingfrom the lung, may be more important as a long range attractant. Reportsby Rahm (Rahm, U. Zum problem der attraktion von stechmucken durch denmenschen, Acta Trop., 13:319-344, 1956) and Brouwer (Brouwer, R. Theattraction of carbon dioxide excreted by the skin of the arm of malariamosquitoes, Trop Geogr. Med. 12:62-66, 1960) showed that carbon dioxideoutput from the skin was insignificant in stimulating mosquitoes. Incontrast to these findings, Khan et al. (Khan, A. A., H. I. Maibach, W.G. Strauss, and W. R. Fenley. Quantitation of effect of several stimulion the approach of Aedes aegypti, J. Econ. Entomology 59:690-694, 1966)concluded that heat and carbon dioxide are important for the approach ofmosquitoes to the host at close proximity, and that odor was moreimportant at greater distance. Carlson et al. (Carlson, D. A., C. E.Schreck, and R. J. Brenner, Carbon dioxide released from human skin:effect of temperature and insect repellents; Journal of MedicalEntomology 29:165-170, 1992) measured the amount of carbon dioxide givenoff by the hand at 1.0-1.8 ml/h under laboratory conditions. The authorsconcluded that this amount of carbon dioxide is negligible compared toambient levels and was unlikely to be attractive to mosquitoes byitself.

In 1958, Brouwer (Brouwer, R., Acad. Proefschr. Leiden, 110p, 1958)reported consistent differences in attraction of Anopheles stephensi tohumans that were independent of moisture, warmth and carbon dioxide. Heconcluded that the differences were due to sweat or body odor. Schreck(Schreck, C. E. and J. James, Broth culture of bacteria that attractfemale mosquitoes, Mosquito News 28:33-38, 1968) reported that apolyethylene glove, worn for 1 hour, remained attractant to mosquitoesover a 3 hour period after removal from the hand. Thompson and Browndemonstrated the attractiveness of sweat was decreased by the release ofvolatile acids (Thompson, R. P. and A. W. A. Brown; The attractivenessof human sweat to mosquitoes and the role of carbon dioxide; MosquitoNews 15:80-84, 1955).

Gilbert et al. studied 50 men and 50 women to determine theirattractiveness to Aedes aegypti mosquitoes (Gilbert, I. H. G. K. Gouckand N. Smith; Attractiveness of men and women to Aedes aegypti andrelative protection time obtained with DEET; The Florida Entomologist49:53-66, 1966). The 50 women subjects were, on average, less attractivethan the 50 men. However, there was considerable overlap in the rangesof attraction, and many of the women were more attractive than some ofthe men. However, only two of the most attractive 10 subjects werewomen, and all of the least attractive 10 were women. A possiblerelationship between attraction and differences in skin lipidcomposition was not investigated. Roessler hypothesized that changes inthe attractiveness of females with the menstrual cycle were caused bychanges in estrogen evaporation from the skin (Roessler, P.; Theattractiveness of steroids and amino acids to female Aedes aegypti;Proceedings of the Fiftieth Annual Meeting, New Jersey MosquitoExtermination Association and Nineteenth Annual Meeting, AmericanMosquito Control Association, Atlantic City, March 1963, pp. 250-255).

In a 1968 report, Acree et al. found a correlation between theattractiveness of individuals to mosquitoes and the quantity of lacticacid present in acetone washings of hands. Attractive material was firstobtained by condensation of a nitrogen stream above the skin. However,the amount of material obtained was too small for analytical methodsavailable at that time. These workers noted that the attractancy oflactic acid was not evident without the presence of carbon dioxide.

Price et al studied the attraction of mosquitoes to human emanations ina dual port olfactometer (Price, G. D., N. Smith and D. A. Carlson; Theattraction of female mosquitoes (Anopheles quadrimaculatus SAY) tostored human emanation in conjunction with adjusted levels of relativehumidity, temperature, and carbon dioxide; J. Chemical Ecology5:383-395, 1979). Mosquitoes (female Anopheles quadrimaculatus SAY) werepreferentially attracted to the “emanation” air, even though excesscarbon dioxide or water had been added to control air withoutemanations.

In 1961, Brown and Carmichael reported that lysine free base was amosquito attractant (Brown, A. W. A. and A. G. Carmichael; Lysine as amosquito attractant; Nature 169:508-509, 1961). Lysine was known to bepresent in human sweat (Hier, S. W. T. Cornbleet and 0. Bergeim; J.Biol. Chem. 166:327, 1946). Although other amino acids had mosquitoattractant properties, they were considerably less attractant thanlysine. The attractiveness of lysine was later found to be proportionalto the presence of carbon dioxide (Lipsitz, E. Y. and A. W. A. Brown;Studies on the responses of the female Aedes mosquito: IX The mode ofattractiveness of lysine and other amino acids; Bull. Entomo. Res. 54675-687, 1964).

Strauss et al., surveyed hospitalized patients with various diseases andtaking various medications for their attractiveness to mosquitoes by amosquito probing technique. No drug, vitamin, or disease was associatedwith unattractiveness, with the possible exception of untreated myxedema(Strauss, W. G. H. I. Maibach and A. A. Kahn; Drugs and disease asmosquito repellents in man; Am. J. Trop Med. Hyg. 17:461-464, 1968).

In addition to the compounds mentioned above, USDA investigators havestudied 1-octen-3-ol as a mosquito attractant (Kline, D. L. D. A. Dameand M. V. Meisch; Evaluation of 1-octen-3-ol and carbon dioxide asattractants for mosquitoes associated with irrigated rice fields inArkansas; J. Am. Mosq. Control Assoc. 7:165-9, 1991). Israeliinvestigators found that although sheep were attractive to Culex pipiensL. and Aedes caspius (Pallas), few Culex pipiens and no Aedes caspiusengorged. The investigators suggested that sheep may possess, inaddition to the mechanical protection afforded by wool, a close-actingrepellent that deters the mosquitoes from biting. The repellent was notidentified.

Maibach and coworkers report the observation that the attractancy ofhuman sweat increased significantly when lipids were removed (Maibach,H. I. A. A. Khan, W. G. Strauss and W. A. Skinner; Human skin inrelationship to mosquito attraction and repulsion; Connecticut Medicine,33:23-28, 1969). Schreck and coworkers isolated a material from glassbeads previously handled by humans (Schreck, C. E., N. Smith, D. A.Carlson, G. D. Price, D. Haile and D. R. Godwin; A material isolatedfrom human hands that attracts female mosquitoes; Journal of ChemicalEcology, 8:429-438, 1981). This residue was found to be attractant tofemale Aedes aegypti and Anopheles quadrimaculatus Say mosquitoes. Thisresidue was characterized as volatile, and stable on refrigeratedstorage for up to 60 days. The residue was not purified or chemicallyanalyzed. Skinner et al. obtained human skin-surface lipids from etherwashings of elbows from a number of volunteers (Skinner, W. A. H. C.Tong, H. I. Maibach and D. Skidmore; Human skin-surface lipid fattyacids—mosquito repellents; Experientia 26:728-730, 1970). This mixturewas found to be repellent to Aedes aegypti mosquitoes. Vacuumdistillation, gas chromatography and thin layer chromatography were usedto isolate components from the mixture. The organic fraction of thelipids contained only weakly repellent unsaturated hydrocarbons, withthe major repellent activity present in the more polar fractions.Straight chain carboxylic acids from C-5 to C-13 were found to haverepellent activity in olfactometer tests; higher homologs from C-14 toC-18 had little repellent activity. Straight chain unsaturatedcarboxylic acids from C-9 to C-24 were also found to have repellentactivity. Skinner concluded that unsaturated fatty acids accounted forthe repellency of the free fatty acid fraction of skin surface lipids,based on two findings: 1) no saturated fatty acids below C₁₃ weredetected and higher homologs had little repellent activity inolfactometer tests, 2) unsaturated fatty acids starting with C₁₄ weredetected and these had repellent activity in olfactometer tests. Skinnerthen suggested that mosquito attraction to animals could be reduced byincreasing the amount of unsaturated fatty acids present on the skinsurface. To this end, 2-decenoic acid was tested for mosquito repellentactivity in volunteers at Letterman Army Institute of Research in 1970(Kurtz, A. P.; More Effective Topical Repellents Against Malaria-BearingMosquitoes: Review of Volunteer Tests of Mosquito repellent FormulationsOctober 1969-September 1971, Report No. 13 (Interim Report), LettermanArmy Institute of Research, Presidio of San Francisco, Calif. 94129, May1, 1973). The compound was applied to the forearm at a dose of 0.5mg/cm² and compared to DEET at the same dose. Application sites werechallenged with Aedes aegypti mosquitoes. Although 2-decenoic acidshowed repellent activity, its average duration of protection wasshorter than that of DEET and its range of protection time was largerthan that of DEET (Table 2). Skinner also reported the evaluation of anumber of unsaturated fatty acids on the skin of man (Table 3). However,none provided longer protection time than DEET. It should be noted thatthis line of investigation was based on fatty acids recovered from skinsurface wipes and not on the skin's chemical vapor, which is responsiblefor host seeking behavior. The significance of the volatile compoundswas therefore underestimated.

TABLE 2 Test of Decenoic acid for repellency against Aedes aegypti onthe skin of man (reference Kurtz, LAIR Report No. 13, 1973)^(a)Protection Time Protection Time Compound (hours) Range (N) Decenoic acid0.5 6 ± 4 0.5-12.5 (14) mg/cm² DEET, 0.5 mg/cm² 8 ± 2 3.5-12.0 (10)^(a)A protection time of 0.5 h, observed for two subjects, indicatedrepellent failure at the first test period.

TABLE 3 Protection time of unsaturated carboxylic acids (0.31 mg/cm²,reference Skinner, W.A., Attractiveness and Repellency of Man toMosquito Bites, DTIC Report No. AD693891, October, 1969) Protection timeagainst Compound Aedes aegypti mosquitoes 2-Nonenoic Acid (unsat C-9) 2h 2-Decenoic Acid (unsat C-10) <15 min. Undecylenic Acid (unsat C-11)3.5 h 2-Dodecenoic Acid (unsat C- 2 h 12) Oleic Acid (unsat C-18) <15min. Linoleic Acid (unsat C-18) <15 min. Linolenic Acid (unsat C-18) <15min. Arachidonic Acid (unsat C-20) <15 min. DEET (reference) 5.5 h

A number of a straight chain carboxylic acids were reported in 1954 tohave repellent activity (King, W. V., Chemicals evaluated asinsecticides and repellents at Orlando, Fla. Agriculture Handbook No.69; Entomology Research Branch, Agricultural Research Service, U.S.Department of Agriculture, Washington, D.C., 1954. p. 185). None,however, provided protection time equal to that of DEET (Table 4).Quintana and coworkers realized the short-comings of these compounds andattempted to improve their protection time by the preparation ofcarboxylic acid esters designed to adhere to the stratum corneum andslowly release the active component (free acid) on hydrolysis of theester (Quintana, R. P., Lasslo, A., Garson, L. R., Chemical Studies inConnection with Potential Systemic Insect-Repellents and ProphylacticAgents Deposited in the Skin; Report No. 4, Research Contract No.DA-49-193-MD-2636, U.S. Army Medical Research and Development Command,Office of the Surgeon General, Washington, D.C. 20315). However, thesecompounds did not result in a repellent with improved duration ofprotection over DEET.

TABLE 4 Protection time of saturated carboxylic acids applied to humanskin at a dose of approximately 2 mg/cm².^(a) Protection Protection timetime against against yellow malaria Compound fever mosquitoes mosquitoesCaproic Acid (C-6) — — Ethanthic (C-7) 121-180 min 90+ min. CaprilicAcid (C-8) — — Pelargonic Acid (C-9) 180+ min. 31-60 min. Capric Acid(C-10) 300+ min. 61-90 min. Hendecanoic Acid (C-11) 300+ min. 90+ min.Lauric Acid (C-12) — — DEET (reference) 363 min^(b) — ^(a)Except wherenoted, data taken from King, 1954, Chemicals evaluated as insecticidesand repellents at Orlando, FLA., U.S. Department of Agriculture,Agricultural Research Service, Agriculture Handbook No. 69). Followingnegative skin-irritation tests on rabbits at the FDA, compounds wereevaluated on the skin of 2 to 4 male human subjects. One ml of thecompound was rubbed over one forearm (approximately 500 cm2). A glovewas worn to protect the untreated hand while the treated # forearm wasexposed in a cage containing a high number (2,000-4,000) of unfedmosquitoes for 3 minutes at intervals of approximately 30 minutes untiltwo bites were received (two bites in one test period or one bite ineach of two consecutive test periods). The time interval betweenapplication and when two bites were received was defined as the“protection time”. Against the yellow fever mosquito (Aedes aegypti(L.)), ethanthic acid (C-7) was rated 3 (121-180 min) pelargonic acid #(C-9) was rated 4 (180+ min), capric acid (C-10) was rated 4A (300+min.) and hendecanoic acid (C-11) was rated 4A (300+ min.). Against themalaria mosquito (Anopheles quadrimaculatus Say), ethanthic acid wasrated 4 (90+ min.), pelargonic acid was rated 2 (31-60 min), capric acidwas rated 3 (61-90 min.) and hendecanoic acid was rated 4 (90+ min.).^(b)Data from Gilbert, I.H., Gouck, H.K. and C.N. Smith. 1957, Newinsect repellent, Soap and Chemical Specialties, 33: 115-133.

In a later report, Skinner et al. analyzed acetone extracted lipids fromskin using gas chromatography-mass spectroscopy (Skinner, W. A., H. C.Tong, H. Johnson, R. M. Parkhurst, D. Thomas, T. Spencer, W. Akers, D.Skidmore and H. Maibach; Influence of human skin surface lipids onprotection time of topical mosquito repellent; J. Pharm. Sci.,66:1764-1766, 1977). Multiple regression analysis was used to relateattractancy and repellent protection time to the amounts of saturatedand unsaturated fatty acids. Dry protection time or duration ofprotection of the insect repellent N,N-diethyl-3-benzamide (DEET)correlated positively with saturated fatty acids C-11, C-13, C-15 andC-18 and unsaturated fatty acids C-14, C-15, C-16 and C-17; dryprotection time correlated negatively with saturated C-7, C-12 and C-16fatty acids. The fatty acids may affect the protection time of DEET by aphysical mechanism; that is, they may alter the evaporation andpenetration of DEET through their film forming activity. Indeed,repellent protection time of DEET correlated positively with the totalweight of lipid found on the skin. Attractancy, as measured by theaverage number of Aedes aegypti mosquitoes probing the test site of thevolunteer in one minute, was found to correlate positively with C-15unsaturated fatty acid and C-14 saturated fatty acid; attractancy wasfound to correlate negatively with the more volatile C-11 saturatedfatty acid. The authors indicated that the precise identification offatty acid components affecting attractiveness would require furtherstudy.

There is ample evidence that human skin emanates both attractant andrepellent compounds for mosquitoes. However, skin emanations have beenpoorly characterized, and important volatile components were lost in theanalysis procedures (Bowen, M. F., The sensory physiology ofhost-seeking behavior in mosquitoes. Annu. Rev. Entomol., 36:139-158,1991). No single compound is likely responsible for mosquito attraction;the same can be said for mosquito repulsion. Although certain fattyacids were found to repel mosquitoes, a practical insect repellent hasnever been developed from these compounds because it was not appreciatedthat optimal evaporation rates from the skin were not achieved. We havedeveloped a long lasting repellent based on a combination of fattyacids, each with the appropriate volatility.

EXAMPLES OF THE INVENTIVE INSECT AND ARTHROPOD REPELLENT EXAMPLE 1:Identification of natural insect repellent compounds on human skin

Olfactometer: A Fiensod and Spielman olfactometer, as modified by Bowenand Davis, measured the host-oriented flight response of femalemosquitoes to volatile host emanations (Feinsod, F. M., and A. Spielman;An olfactometer for measuring host-seeking behavior of female Aedesaegypti (Diptera:Culicidae); J. Med. Entomol., 15:282-285, 1979). Theolfactometer (approximately 38 cm high) consisted of an upper and lowerscreened chamber with a closure between the chambers (FIG. 8). A fanplaced above the upper chamber drew air through the apparatus atapproximately 0.2 m/s. A temperature and humidity controlled chamber (5′wide by 6′ long by 8′- high) was constructed to house the test subjectand the olfactometer.

Rearing of Mosquitoes: A second environmental chamber, maintained at 27°C. and 80% humidity, was dedicated to the rearing of Aedes aegyptimosquitoes. Routine shipments of eggs (American Biological Supply,Gainesville, Fla.) were used to maintain a continuous supply of adult5-10 day old mosquitoes.

Assays for Attraction of Mosquitoes to Human Subjects: A group of 30volunteers, consisting of 14 females and 16 males and ranging in agefrom 24 to 68 years, was selected from the surrounding civilianpopulation. Individuals were tested for their ability to attract Aedesaegypti mosquitoes contained in the olfactometer. Tests were conductedat a temperature of 27° C. and 50% relative humidity. For each trial 15avid adult female Aedes aegypti mosquitoes (5-10 days post-emergence)were placed in the upper chamber. A small fan was placed on top of theupper chamber to cause an air flow from the lower chamber to the upperchamber. A trial began when the closure between the upper and lowerchamber was opened in the absence of a human host. The number ofmosquitoes entering the lower chamber within a 3 minute period wasrecorded. The volunteer then placed his or her arm beneath the lowerchamber and the number of mosquitoes flying from the upper chamber tothe lower chamber was recorded for the time intervals 0-1, 1-3, 3-5 and5-7 minutes. This trial was repeated twice during a test session toobtain three replicates. Two additional test sessions, at time intervalsof at least 1 week, were conducted to obtain at least 8-9 replicates foreach of 24 subjects. Of the remaining 6 subjects, 3 were tested on twoseparate occasions for a total of 6 replicates per subject; 3 weretested on one occasion for a total of 3 replicates per subject. A totalof 254 tests were conducted.

Olfactometer scores were calculated for each trial by dividing thenumber of mosquitoes entering the lower chamber of the olfactometerduring the 0-1, 1-3, 3-5 and 5-7 minute intervals by the number ofmosquitoes remaining in the upper chamber of the olfactometer at the endof the 3 minute control period. The fractions so obtained was plottedversus time. An equation was fitted to the data and the area under thecurve (olfactometer score) was calculated. An area of 0 (0 mosquitoesentering the lower chamber ×7 minutes) would indicate the subject wascompletely unattractive to mosquitoes. A area of 7 would indicatemaximum attraction.

Human subjects were identified from a group of 30 males and femaleswhose forearms were consistently least attractive to Aedes aegyptimosquitoes contained in an olfactometer (Table 5). Subjects were alsoidentified who were consistently most attractive to mosquitoes (Table5). All of the 4 least attractive subjects were female and 10 of the 12least attractive subjects were female. All of the 5 most attractivesubjects were male and 10 of the 12 most attractive subjects were male.Females in general were significantly less attractive to the mosquitoesthan the males (ANOVA, F=49.33, P=0.0000). The histograms ofolfactometer response for all trials with female subjects is given inFIG. 9. The corresponding data for male is given in FIG. 10.Olfactometer response did not significantly correlate (P>0.05) with ageof male or female subjects (FIGS. 11 and 12).

TABLE 5 Olfactometer response of 30 human subjects to mosquitoes. No. ofSubject No. Olfactometer Response^(a) Replicates 30 (Female)^(b) 1.73 ±0.67  3^(c) 24 (Female)^(b) 2.13 ± 1.13 9 15 (Female)^(b) 2.65 ± 0.53 829 (Female)^(b) 2.79 ± 1.44 9 18 (Female) 3.01 ± 1.19 9 26 (Male) 3.06 ±0.97 9 16 (Female) 3.26 ± 1.10 9 1 (Female) 3.34 ± 1.35 18  3 (Male)3.47 ± 1.52 10  27 (Female) 3.56 ± 1.39 9 11 (Female) 3.60 ± 1.19 9 28(Female) 3.65 ± 0.53 6 25 (Male) 3.67 ± 1.49 6 23 (Male) 3.82 ± 1.05 912 (Female) 4.08 ± 1.18 9 10 (Female) 4.22 ± 1.63 3 22 (Male) 4.25 ±0.92 9 17 (Male) 4.33 ± 0.94 9 6 (Female) 4.39 ± 1.51 9 13 (Male) 4.44 ±1.36 9 5 (Male) 4.45 ± 0.62 9 20 (Male) 4.74 ± 0.68 9 4 (Female) 4.92 ±0.88 9 19 (Male) 4.93 ± 0.99 3 21 (Male) 5.03 ± 0.84 6 14 (Male)^(b)5.06 ± 1.11 9 7 (Male)^(b) 5.20 ± 1.11 9 9 (Male)^(b) 5.21 ± 0.85 9 2(Male)^(b) 5.31 ± 0.73 11  8 (Male)^(b) 5.32 ± 0.76 9 ^(a)Olfactometerresponse (mean ± S.D.) was calculated as the area under the curve offractional mosquito response versus time profile. A hypothetical testsubject completely unattractive to mosquitoes would have a score ofzero. A maximally attractive subject would have a score of almost seven.^(b)Olfactometer response scores were analyzed by ANOVA and theStudent-Newman-Keuls Multiple Range Test, which identified subjects Nos.15, 24, 29, and 30 as least attractive to mosquitoes and subjects Nos.2, 7, 8, 9, and 14 as most attractive to mosquitoes. Each of the fourleast attractive female subjects were significantly different from allof the five most attractive male subjects (Tukey's test, P < 0.05).^(c)Subject 30 was retested on a separate occasion with even lowerolfactometer scores; however, the mosquitoes were exposed to lowtemperatures from an equipment malfunction and the results are notincluded.

EXAMPLE 2: Assay of Compounds for Mosquito Repellency on Gauze orPolyester Film

Test compounds were dissolved in acetone or ethanol at a concentrationof 150 mg/5 cc. Ethanol solutions of carboxylic acids were prepared justprior to use. Five hundred microliters of these solutions were appliedto a 50 cm² circular area of a single layer of cotton gauze (CurityCurad gauze, Futuro Inc., Milford, Ohio) or nonwoven polyester film(Reemay 2250, Reemay/Tycon, Inc.). The resultant dose was 0.3 mg/cm².Treated gauze or film was allowed to dry in a hood for 3 minutes priorto placement in a cylindrical stainless steel cup (9 cm in diameter and3 cm in height), whose bottom consisted of stainless steel screen. Thecup was attached to the bottom of the olfactometer (FIG. 8) so that airflowed through the stainless steel screen of the cup, through thetreated gauze or film, and through the olfactometer. A volunteer'sforearm was placed under the cup, so that air drawn into the cup andolfactometer was laden with human skin emanations. Tests were conductedas described in the preceding paragraph, “Assays for attraction ofmosquitoes to human subjects”. Percent repellency was determined fromthe fraction of mosquitoes entering the lower chamber over a sevenminute period.

This assay is an approximate measure of the intrinsic repellency of acompound. Good repellency in this test is a necessary, but notsufficient, condition for good repellency on skin. Mosquito repellentsmust produce a vapor over the skin surface to confuse the host seekingbehavior of the insect. However, volatilization must not be so greatthat the repellent action rapidly dissipates. Since volatilization fromthe skin will be different from an inanimate surface, skin tests arenecessary to confirm that a compound will be a practical repellent.

Percent repellency results for various compounds are contained in Table6. Three of the compounds tested (3M2OCTEN, 3M2PENTEN, and valerolactam)were found only on the skin of females (Zeng, X. Leyden, J. J. Spielman,A. I. and Preti, G., 1996, Analysis of characteristic human femaleaxillary odors: qualitative comparison to males; J. Chem. Ecol.22:237-257). 3M2OCTEN exhibited the greatest repellency (95%), 3M2PENTENrepellency (65%) was similar to that of DEET (74%), and valerolactam hadessentially no repellent activity (20%).

TABLE 6 Percent repellency for various compounds (applied to cottongauze or polyester film at a dose of 0.3 mg/cm²) against Aedes aegyptimosquitoes^(a). Carbon Percent Test Compound Atoms Repellency N Ethanol2 7 ± 9 5 Acetone 3 12 ± 10 12  Pentanoic acid^(b) (C-5) 5 not tested —(valeric acid) 2-Pentenoic Acid 5 100 ± 0  2 (2PENTEN) Valerolactam 5 20± 22 3 3-Methylpentanoic Acid 6 43 ± 14 2 (3MPENTAN)3-Methyl-2-pentenoic 6 65 ± 16 3 Acid (3M2PENTEN) Octanoic Acid (C-8) 887 ± 1  2 2-Octenoic Acid (2- 8 97 ± 5  2 OCTEN) 4-Methyloctanoic acid 988 ± 18 2 (4MOCTAN) 3-Methyl-2-octenoic acid 9 95 ± 6  6 (3M2OCTEN)Nonanoic acid (C-9) 9 97 ± 5  2 Decanoic acid (C-10) 10  100 ± 0  2Undecanoic acid (C-11) 11  93 ± 0  2 Lauric acid (C-12) 12  69 ± 23 3N,N-Diethyl-m-toluamide 12  74 ± 12 3 (DEET) ^(a)Tests were conducted 3minutes after application of test compounds. ^(b)Pentanoic acid was nottested because of its highly offensive odor.

All of the octanoic acid derivatives had good repellent activity, in therange of 87-97% repellency. The pentanoic acid derivatives weregenerally less repellent (43-65%); however, 2-pentenoic acid had 100%repellency. Nonanoic acid (C₉ straight chain), decanoic acid (C₁₀straight chain), and undecanoic acid (C₁₁ straight chain) had goodrepellency (93-100%). Lauric acid (C₁₂ straight chain) had lowerrepellency (69%), similar to DEET. Mosquito repellent activity has notbeen previously reported for the octanoic acid derivatives 3M2OCTEN,2OCTEN, 4MOCTAN, and the pentanoic acid derivatives 3M2PENTEN, 2PENTEN,and 3MPENTAN. Repellent activity has been reported for the straightchain saturated carboxylic acids and certain unsaturated carboxylicacids (See Tables 2, 3 and 4). Some of the saturated carboxylic acidshave also been investigated as mosquito attractants (Knols, B. G. J.,1996, Odour-mediated host-seeking behavior of the afro-tropical malariavector Anopheles Gambiae Giles; Thesis. ISBN: 90-5485-487-1; WageningenAgricultural University; The Netherlands; pp. 213). The results,however, were inconclusive.

In addition to carboxylic acids, alkanes, alkenes, alcohols, aldehydes,ketones, acids and lactones are known to exist on the skin surface(Zeng, X., Leyden, J. J., Lawley, H. J., Kiyohito, S., Isao, N., andPreti, G. 1991, Analysis of characteristic odors from human maleaxillae, Journal of Chemical Ecology, 17:1469-1492) or to volatilizefrom the skin surface (Goetz, N., Kaba, G. Good, D. Hussler, G. andBore, P., 1988, Detection and identification of volatile compoundsevolved from human hair and scalp using headspace gas chromatography,Journal of the Society of Cosmetic Chemists, 39:1-13). Repellentactivity is known to exists in alcohols, aldehydes, ketones, acids(King, W. V., Chemicals evaluated as insecticides and repellents atOrlando, Fla., U.S. Department of Agriculture, Agricultural ResearchService, Agriculture Handbook No. 69) and lactones (Weeks, M. H. andDeSena, B. J. Topical Hazard Evaluation Program of Candidate InsectRepellent AI3-36030 delta-Dodecalactone, U.S. Army Environmental HygieneAgency, Aberdeen Proving Ground, Md., Defense Technical InformationReport No. ADA 040974, March 1976-April 1977).

EXAMPLE 3: Assay of Compounds for Mosquito Repellency on Skin

Test compounds were dissolved in acetone or ethanol at a concentrationof 300 mg/5 cc. Ethanol solutions of carboxylic acids were prepared justprior to use. Three hundred and fifty microliters of these solutionswere applied to a 70 cm² rectangular area of the forearm. The resultantdose was 0.3 mg/cm². The repellent treated area was allowed to dry for 5minutes prior to test. The treated skin area was placed under theolfactometer and tests were conducted as described in the precedingparagraph, “Assays for attraction of mosquitoes to human subjects”.Percent repellency was determined from the fraction of mosquitoesentering the lower chamber over a seven minute period.

A number of compounds were preliminarily investigated for their abilityto act as mosquito repellents after topical application (Table 7). Someof the more volatile acids (octanoic acid and 4MOCTAN) had meanrepellency (87-93%) that was competitive with that of DEET (95%) shortlyafter application (0 hr). At 2 hours after application, DEET repellencyremained high (89%), while the highest repellency for carboxylic acids(66-73% mean repellency) was found in three of the acids containing 9carbons (3M2OCTEN, 4MOCTAN, and nonanoic acid). The pentanoic acidderivatives were not tested because two of the derivatives had lowrepellency on the gauze/polyester film tests (Table 6) and because thesederivatives are considerably more volatile that DEET (Table 7). Thecompound 2-ethyl-1,3-hexanediol, once a commercial insect repellent, istwice as volatile as DEET and protects against mosquitoes for 3-4 hoursas compared to 5-6 hours for DEET (Hill, J. A., Robinson, P. B., McVey,D. L., Akers, W. A., and Reifenrath, W. G. 1979; Evaluation of mosquitorepellents on the hairless dog; Mosquito News (Journal of the AmericanMosquito Control Association), 39:307-310). Therefore, the pentanoicacid derivatives, having volatilities 17-30 times that of DEET, were notexpected to provide long lasting repellency; these compounds are toovolatile and serve as an upper bound of vapor pressure for a practicalrepellent for carboxylic acids. Decanoic, undecanoic, and dodecanoicacids were less volatile than DEET and had lower 0-h repellency thanDEET (Table 7). Dodecanoic acid demonstrated no repellent effect on skin(Table 7), despite having 93% repellency after application togauze/polyester film (Table 6). This compound was probably notsufficiently volatile from skin and provided a lower bound of vaporpressure for a practical repellent for carboxylic acids.

TABLE 7 Percent repellency for various compounds at various times afterapplication against Aedes aegypti mosquitoes^(a) Carbon PercentRepellency (N) Compound Atoms Vol.^(b) 0 h 2 h 4 h 8 h No 0 — 9 ± 7 (4)13 ± 12 (3) 4± 6 (2) 17 Treatment (1) 2-Pentenoic 5 92 — — — — acid(est) (2PENTEN) 3-Methyl-2- 6 49.5 — — — — pentenoic (est) acid(3M2PENTEN) 3-Methypen- 6 49.5 — — — — tanoic acid (est) (3MPENTAN)Hexanoic 6 39.6 — — — — acid Octanoic 8 10.8 93 (1) 36 (1) — — acid(C-8) 2-Octenoic 8 10.8 50 (1) 29 (1) 27 (1) — acid (2- (est) OCTEN)2-Ethyl- 8 6 — — — — 1,3- hexanediol (6-12) 3-Methyl-2- 9 6 (est) 70 ±24 (2) 40 ± 5 (3) 47 ± 21 60 octerioic (3) (1) acid, 0.3 mg/cm²(3M2OCTEN) 3-Methyl-2- 9 6 (est) 66% (1) 73% (1) 40 (1) — octenoic acid,0.6 mg/cm² (3M2OCTEN) 4-Methyloc- 9 6 (est) 87 (1) 66 (1) — — tanoicacid (4MOCTAN), 0.3 mg/cm² 4-Methyloc- 9 6 (est) 93 ± 0 (2) 79 ± 21 (2)67 ± 9 — tanoic acid (2) (4MOCTAN), 0.6 mg/cm² Nonanoic 9 4.8 76 ± 14(2) 66 (1) 47 (1) — acid (C-9) N,N- 12  3 95 ± 6 (3) 89 ± 10 (3) 83 ± 9— Diethyl-m- (3) toluamide (DEET) Decanoic 10  2.4 73 (1) 53 (1) 73 (1)— acid (C-10) 2-Decenoic 10  2.4 (est) — — — — acid (2DECEN) Ondecanoic11  1.5 (est) 40 (1) — — — acid (C-11) Dodecanoic 12  0.57 0 (1) — — —acid (C-12) (est) ^(a)Compounds applied at a dose of 0.3 mg/cm², unlessotherwise indicated, to one subject. ^(b)Vapor pressure in mm Hg at 125°C. Values were obtained from the literature (Handbook of Chemistry andPhysics, 1996; D. R. Lide and H. P. R. Frederikse, eds., 76th ed., CRC,Boca Raton, pp. 6-77 to 6-108; and Blame, R. L. and Levy, P. F., 1974,The use of thermal evolution analysis (TEA) for the determination ofvapor pressure of agricultural chemicals, Anal. Calorimetry 3: 185-198).Certain values designated “(est)” were estimated or extrapolated fromliterature values.

EXAMPLE 4: Design of Long Lasting Repellent Formulation

Octanoic acid, the eight carbon fatty acid, had the highest volatilityof any of the carboxylic acids tested on skin (Table 7) and provided thebest initial repellency (0-h). However, octanoic acid's repellencyrapidly decayed to only 36% at 2-h and reflected the exponential orfirst order evaporative loss of the compound from the skin surface. Theexponential change in the evaporation rate of DEET from the surface ofexcised pig skin is given in FIG. 13. The change in the evaporation rateof, for example, octanoic acid from the skin surface would be evengreater because it is more volatile than DEET. A repellent is onlyeffective while the evaporation rate is greater than its MEER (minimumeffective evaporation rate). For DEET that is between about 10 and 15μgm/cm²⁻hr, as shown by the straight line in FIG. 13. An impracticallylarge increase in the initial dose, or application level, would berequired to extend protection time of molecule with a high evaporationrate. FIG. 13 also shows the change in the evaporation rate of the novelinventive repellent, formulated with equal parts octanoic, nonanoic, anddecanoic acids. In contrast to DEET, the inventive repellent's change inevaporation rate levels off above the MEER.

Decanoic acid, the ten carbon fatty acid, had the lowest volatility ofany carboxylic acid which provided at least 50% protection at 0-h. Incontrast to octanoic acid, its protection remained relatively constant(Table 7), and reflected its constant or zero order evaporative lossfrom the skin surface (FIG. 13). Because of the compound's lowvolatility, it is not possible to significantly increase its evaporationrate from the skin surface merely by increasing the dose. Such acompound may provide a long duration of protection if its evaporationrate is just above the MEER or may fail immediately if its evaporationrate is just below the MEER. Test results for decenoic acid, a compoundof similar volatility, are illustrative (Table 2). On two of the testsubjects, the repellent failed immediately, while giving up to 12 hoursof protection for other subjects.

The results for the nine carbon nonanoic acid (Table 7) are intermediatebetween the extremes of octanoic acid and decanoic acid. It is lessrepellent than octanoic acid at 0-h, but its repellency does not decayas rapidly. Increasing the dose of related nine carbon acids (3MOCTENand 4MOCTAN) did not result in a significant increase in repellency thatwas competitive with DEET's at 4 hours (Table 7).

It was known that a mixture of two repellents will decrease theirinitial rate of evaporation and provide a higher level of evaporation atlonger time points (Reifenrath et al., 1989, Evaporation and skinpenetration characteristics of mosquito repellent formulations, Journalof the American Mosquito Control Association, 5:45-51). Based on thispremise, repellents were made having a mixture of the eight, nine andten carbon acids would provide long lasting protection. Test results(Table 8) for this mixture gave protection at 8 hours equivalent to thatof DEET at 4 hours.

TABLE 8 Comparison of repellency (% repellency against Aedes aegypti) ofN,N-diethyl-m-toluamide (DEET, 0.3 mg/cm², N = 3) and a mixture ofn-octanoic, n-nonanoic, and n-decanoic acids (C8C9C10, 0.2 mg/cm² each,N = 3) on skin. % % % % Test Repellency Repellency Repellency RepellencySubstance (0 hr) (2 hr) (4 hr) (8 hr) C8C9C10 93 ± 1 85 ± 4  70 ± 19 82± 26 DEET^(a) 95 ± 6 89 ± 10 83 ± 9  — ^(a)Data for DEET taken fromTable 7.

EXAMPLE 5: Mildness Additive for Formulations

Application of octanoic acid full strength to intact or abraded rabbitskin for 24 hours under occlusion produced moderate to severeirritation; full strength nonanoic acid produced moderate irritation;full strength decanoic acid produced moderate to severe irritation(Moreno, O. M., Reports to Research Institute for Fragrance Materials,Aug. 2, 1976, Aug. 22, 1977). When tested at 1% in petrolatum on theskin of human subjects, octanoic and decanoic acids produced noirritation or sensitization reactions. When tested at 12% in petrolatumon the skin of human subjects, nonanoic acid produced no irritation orsensitization reactions. Erythema was observed on the skin of humanmales after repeated applications of 0.5 M solutions of octanoic,nonanoic and decanoic respectively) under occlusive conditions(Stillman, M. A., Maibach, H. I. and Shalta, A. R., Relative irritancyof free fatty acids of different chain length. Contact Dermatitis1:65-69, 1975).

Solutions containing 5% octanoic acid, 5% nonanoic acid, and 5% decanoicacid (C8C9C10) in ethanol and volatile silicone fluid (Dow Corning 345fluid, CTFA designated cyclomethicone) were prepared. An aqueous gelcontaining 5% of each acid was also prepared. Their skin irritancy wascompared to that of a commercial insect repellent (cream formulation of10% DEET, Skintastic, S. C. Johnson, Racine WHEREIN) on the forearms ofa male subject. C8C9C10 in alcohol and silicone solutions were appliedat a volume of 0.5 ml to gauze pads that were placed on separate 1inch×1 inch areas of skin; the C8C9C10/gel and DEET/cream formulationswere applied at a mass of 0.5 g to separate sites. All sites werecovered with a semi-occlusive tape (Transpore, 3M, Minneapolis, Minn.).Four hours after applications, sites were uncovered and washed withwater. No erythema was observed with the C8C9C10/silicone formulationand slight erythema was observed with the DEET cream formulation; noerythema was observed at later time points (24, 48, 72 hours afterapplication) for these two formulations. In contrast, theC8C9C10/aqueous gel formulation caused a burning sensation afterapplication and this formulation, along with the C8C9C10/alcoholformulation resulted in erythema, sometimes severe, at 4, 24, 48 and 72hours.

A Primary Dermal Irritation study of C8C9C10/silicone formulation andthe commercial DEET cream formulation was conducted on six rabbitsaccording to EPA, FIFRA Subdivision F guidelines. The protocol wassimilar to that outlined for the human exposure, except that applicationsites were totally occluded with a rubber dam for 4 hours. Bothformulations were rated as mildly irritating in this test.

Octanoic, nonanoic and decanoic acid clearly have the potential to causeskin irritation and the degree of skin irritation will be a function ofthe formulation. Alcohol and aqueous gel formulations containing 5% ofeach acid do not appear acceptable for use as an insect and arthropodrepellent in humans; a the silicone formulation however was found to beacceptable.

In addition to having the effect of reducing skin irritation, waterinsoluble silicon containing additives are known to impart waterrepellency to a topical formulation (Dow Corning Literature Code2223926, Dow Corning Corporation, Midland, Mich.).

Volatile silicon fluids are available commercially. For example, DowCorning uses commercial designations of 244, 245, 246, 344 and 345,which are mixtures of polydimethylcyclosiloxanes (cyclomethicones) andare composed of tetramers (e.g. cyclotetrasiloxane,octamethylcyclotetrasiloxane), pentamers (e.g. cyclopentasiloxane,decamethylcyclopentasiloxane), and hexamers (e.g. cyclohexasiloxane,dodecamethylcyclohexasiloxane).

The volatility of the vehicle can be important as well as the volatilityof the active ingredients. The cyclomethicones are more volatile thantypical repellent molecules, and are slightly less volatile than water.The cyclomethicones have a long history of use in cosmetic preparations.As vehicles, they allow good spreading of actives on the skin and willeventually evaporate. They are insoluble in water, so that resistance towater wash-off of actives is imparted. The cyclomethicones can be turnedinto gels for ease of application to the skin. Gelling of a formulationof octanoic, nonanoic, and decanoic acids (5% each in 344 fluid) did notinterfere with repellent activity against mosquitoes in tests conductedas described in Example 3.

Dimethicone (hexamethyldisiloxane) has similar physical properties tothe cyclomethicones and is also extensively used in cosmetics. A varietyof polydimethylsiloxanes, with higher molecular weight than thecyclomethicones or dimethicone, enjoy wide use in cosmetics; however,because of their higher molecular weight, they are less volatile. Theydo provide alternative carriers to the cyclomethicones, or mixtures ofthe two can be used.

A wide variety of derivatives of the above compounds are obtained byintroduction of various functional groups, by copolymerization, or bycrosslinking and many of those can be used to make useful formulationsof the inventive insect and arthropod repellent.

Mixtures of the various silicone fluids, either with other siliconefluids or non-silicon containing substances, are used in a variety ofcosmetic preparations to impart special properties, to include waterrepellency and skin protection.

To insure that the addition of silicone fluid to the actives did notinterfere with mosquito repellency, a comparison of the C8C9C10/siliconeformulation with a commercial insect repellent formulation wasconducted. A commercial formulation of DEET (Skintastic, S. C. Johnson,Racine,) was applied to a 100 cm² area on the forearm of 1 volunteer(subject 02) to give a dose of 0.3 mg/cm² of DEET. A formulation ofC8C9C10 (5% octanoic, 5% nonanoic, 5% decanoic in Dow Corning 345volatile silicone fluid) was applied to a 100 cm² on the subject's otherarm to give a dose of 0.3 mg/cm² total acids. Application sites wereplaced under the olfactometer at 1, 2 and 4 hours after treatment.Untreated areas on each arm were placed under the olfactometer at thecompletion of the treated area tests to check the avidity of themosquitoes. Tests were done on four separate test days. The results areshown in FIG. 14. The inventive C8C9C10/silicone formulation hadrepellency equal to the commercial formulation at the 1, 2 and 4 hourpoints (ANOVA, Tukey Studentized Range Method, P=0.05). Interestingly,C8C9C10/silicon at 0.3 mg/cm² total actives produced repellency (90±13%at 1 h, 81±14% at 2 h, and 74±22% at 4 hours) equal to unformulatedC8C9C10 applied at 0.6 mg/cm² total actives (Table 8).

Thus, the invention provides a new formulation for use on human skin torepel insects and arthropods. The formulation is based on chemicalsnormally found on the human skin and so has a natural feel. It combinescarbon chains having insect repellent activity at different vaporpressures, to achieve persistence over time on the skin and volatilityfor effectiveness in the volume of air surrounding the skin.

EXAMPLE 6: Veterinary Uses

Animal productivity is known to be reduced as a result of biting insectsand arthropods. For example, stable flies reduce milk production by 5 to10%. While the use of pesticides can sometimes provide a short termsolution to this problem, the long term economic consequences of damageto non-target species, environmental pollution, and contamination of thefood chain can be severe. The C8C9C10/silicone formulation provides anon-lethal and non-toxic method to protect animals as well as humansfrom nuisance and disease-carrying insects. This formulation is suitablefor use in standard hand-held sprayers and would imparts waterrepellency.

Specifically, formulation of C8C9C10 (5% octanoic, 5% nonanoic, 5%decanoic acids) in Dow Corning 345 fluid was applied to membranesexposed to approximately 50 wild Stomoxys calcitrans (biting stable fly)contained in plastic tubes 8.5 cm tall and 5 cm in diameter. Themembranes were mounted over warm defribrinated sheep blood. Untreatedmembranes served as controls. Flies were observed for 15-20 minutes,anesthetized, placed on a chill table, and sorted according to whetherthey had engorged blood or not. No flies engorged blood when the freshlytreated membrane was tested and most flies became incapacitated;approximately 90% of flies exposed to the control membrane engorged(Table 9). A membrane treated with the repellent formulation 3 hoursprior to stable fly challenge also prevented all flies from engorging;approximately 50% of flies exposed to the control membrane engorged(Table 9).

TABLE 9 Efficacy of formulation C8C9C10/DC345 (5% octanoic, 5% nonanoic,5% decanoic acids in Dow Corning 345 fluid) to prevent engorgement ofstable flies*. Pretreatment Percent Trial No. time interval TreatmentEngorgement 1 0 h C8C9C10/DC345 0% 2 0 h None (control) 94%  3 3 hC8C9C10/DC345 0% 4 3 h None (control) 52%  *A different type of membranewas used in trials 3 and 4, which reduced the number of engorging fliesfor control trial 4.

The inventive insect and arthropod repellent, formulated in a volatilesilicone fluid, was shown to repel and incapcitate stable flies. Thisfinding demonstrated that repellency was not limited to mosquitoes, butextends to other biting flies, insects, or arthropods thus demonstratingthe utility of the novel insect and arthropod repellent for protectingpets and livestock as well as humans.

In summary, the present invention describes a novel insect and arthropodrepellent that provides long lasting protection against mosquitoes, andthat is stable, commercially available, economically competitive, safe(noted GRAS by the FDA).

The description of illustrative embodiments and best modes of thepresent invention is not intended to limit the scope of the invention.Various modifications, alternative constructions and equivalents may beemployed without departing from the true spirit and scope of theappended claims.

What is claimed is:
 1. A method for repelling insects away from a humanor an animal, the method comprising: obtaining an insect repellantcomposition comprising a) a dermatologically acceptable carrier, and b)active ingredients consisting essentially of a mixture of fatty acids,each of the fatty acids having a straight carbon chain of 6 to 12 carbonatoms long, wherein the mixture of fatty acids includes (i) a firstfatty acid molecule having 6 to 8 carbon atoms, and a carboxylic acidgroup, (ii) a second fatty acid molecule having 8 to 9 carbon atoms, anda carboxylic acid group, and (iii) a third fatty acid molecule having 9to 12 carbon atoms, and a carboxylic acid group, wherein the first fattyacid molecule, the second fatty acid molecule, and the third fatty acidmolecule are all different, are in about a 1:1:1 ratio by weight in theactive ingredients, and are in the insect repellent composition in anamount effective to repel more insects away from a test subject that hasbeen treated with the insect repellant composition than a controlsubject without the insect repellant composition after about 3 hours ormore; and applying the insect repellant composition to the human or theanimal to repel insects.
 2. The method of claim 1, wherein the activeingredients consist essentially of about 10 to 90 % by weight of thefirst fatty acid molecule, about 10 to 90 % by weight of the secondfatty acid molecule, and about 10 to 90 % by weight of the third fattyacid molecule, wherein the weight percentages of the first, second, andthird fatty acid molecules are based on the weight of the activeingredients.
 3. The method of claim 1 wherein the dermatologicallyacceptable carrier comprises silicone.
 4. The method of claim 1 whereinapplying the insect repellent composition comprises applying a topicaldose of the insect repellent composition to the human or the animal,wherein the topical dose includes about 0.3 mg/cm²or more of the activeingredients.
 5. The method of claim 1 wherein the insects are bitingstable flies.
 6. The method of claim 1 wherein the animal is livestock.7. The method of claim 1 wherein: the first fatty acid molecule isoctanoic acid, the second fatty acid molecule is nonanoic acid, and thethird fatty acid molecule is decanoic acid.
 8. The method of claim 1wherein the active ingredients consist of the first fatty acid molecule,the second fatty acid molecule, and the third fatty acid molecule. 9.The method of claim 1 wherein applying the insect repellent compositionto the human or the animal comprises applying the insect repellentcomposition to livestock, and wherein the method further comprises:repelling insects away from the livestock for at least about 3 hours.10. The method of claim 9 wherein the active ingredients consistessentially of about 10 to 90 % by weight of the first fatty acidmolecule, about 10 to 90 % by weight of the second fatty acid molecule,and about 10 to 90 % by weight of the third fatty acid molecule, whereinthe weight percentages of the first, second, and the third fatty acidmolecules are based on the weight of the active ingredients.
 11. Themethod of claim 1 wherein the insects are files.
 12. The method of claim1 wherein the insects are mosquitoes.
 13. A method for repelling fliesor mosquitoes away from a human or an animal, the method comprising:obtaining an insect repellant composition comprising a) adermatologically acceptable carrier, and b) active ingredientscomprising (i) octanoic acid, (ii) nonanoic acid, and (iii) decanoicacid, wherein the octanoic acid, nonanoic acid, and decanoic acid are inthe insect repellant composition in an amount effective to repel moreflies or mosquitoes away from a test subject that has been treated withthe insect repellant composition than a control subject without theinsect repellant composition after about 3 hours or more, and whereinthe octanoic acid, the nonanoic acid, and the decanoic acid are in abouta 1:1:1 ratio by weight in the active ingredients; and applying theinsect repellant composition to the human or the animal to repel fliesor mosquitoes.
 14. The method of claim 13 wherein applying the insectrepellent composition comprises applying the insect repellentcomposition to the animal.
 15. The method of claim 13 wherein thedermatologically acceptable carrier comprises silicone.
 16. An insectrepellent composition comprising: a) a dermatologically acceptablecarrier; and b) active ingredients consisting of a mixture of fattyacids, each of the fatty acids having a straight carbon chain 6 to 12carbon atoms long, wherein the mixture of fatty acids is (i) a firstfatty acid molecule having 6 to 8 carbon atoms, and a carboxylic acidgroup, (ii) a second fatty acid molecule having 8 to 9carbon atoms, anda carboxylic acid group, and (iii) a third fatty acid molecule having 9to 12 carbon atoms, and a carboxylic acid group, and wherein the firstfatty acid molecule, the second fatty acid molecule, and the third fattyacid molecule are all different, are in about a 1:1:1 ratio by weight inthe active ingredients, and are in the insect repellent composition inan amount effective to repel more insects away from a test subject withthe insect repellent composition than a control subject without theinsect repellant composition after about 3 hours or more.
 17. The insectrepellant composition of claim 16 wherein the insect repellentcomposition that is on the test subject has a surface concentration ofthe active ingredients of about 0.3 mg/cm² or more.
 18. The insectrepellent composition of claim 16 wherein the first fatty acid moleculeis octanoic acid and the third fatty acid molecule is decanoic acid. 19.An insect repellent composition comprising: a) a dermatologicallyacceptable carrier; and b) active ingredients comprising (i) octanoicacid, (ii) nonanoic acid, and (iii) decanoic acid, wherein the octanoicacid, the nonanoic acid, and the decanoic acid are in the insectrepellent composition in an amount effective to repel more flies ormosquitoes away from a test subject that has been treated with theinsect repellant composition than a control subject without the insectrepellant composition after about 3 hours or more, and wherein octanoicacid, nonanoic acid, and decanoic acid are in about a 1:1:1 ratio byweight in the active ingredients.
 20. The insect repellant compositionof claim 19 wherein octanoic acid, nonanoic acid, and decanoic acid areeach in the insect repellent composition in an amount of about 10 toabout 90% by weight of the active ingredients.
 21. The insect repellantcomposition of claim 19 wherein the insect repellent composition that ison the test subject has a surface concentration of the activeingredients of about 0.3 mg/cm² or more.
 22. The insect repellentcomposition of claim 19 wherein the active ingredients consistessentially of the octanoic acid, the nonanoic acid, and the decanoicacid.